Potent coatings for stents

• US 20030088307A1
• Filed: 05/16/2002
• Published: 05/08/2003
• Est. Priority Date: 11/05/2001
• Status: Abandoned Application

• Current Assignee: Biosensors International Group, Ltd.
• Original Assignee: Biosensors International Group, Ltd.
• Inventors: Savage, Douglas R., Betts, Ronald E., Shulze, John E.
• Application Number:
  US10/150,909
• Publication Number:
  US 20030088307A1
• Time in Patent Office: Days
• US Class Current: 623/1.15
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2002/91558 connected peak to peak
• CPC Class Codes: A61F 2230/0054 V-shaped
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A stent having an expandable stent body with a generally tubular shape comprises a series of support surfaces upon which a polymer stent coating has been applied. One or more bioactive agents are disposed within the coating. The coating is applied by evaporating solvent from a solution which has been applied to the stent surfaces from a pressurized reservoir or positive displacement pumping means attached to a delivery tube. The delivery tube'"'"'s longitudinal or X-Y-Z position along the body of the stent, the rotation of the stent along its longitudinal axis, and the delivery rate are coordinated by a programmable controller to deposit precise and repeatable amounts of polymer and agent on the stent surfaces. Preferably, an anti-restenosis agent consisting of a potent analogue or derivative of tranilast are disposed in a bioerodable stent coating, comprising poly(lactic acid), or, alternatively, in a biodurable stent coating comprising EVA.

Claims

1. A stent comprising:

an expandable stent body having a generally tubular shape;

a plurality of support surfaces on said stent body upon which a coating is applied, said coating containing one or more bioactive agents disposed therein, wherein at least one of said bioactive agents is a potent derivative of Tranilast.

2. The stent of claim 1, wherein said derivative is a diarylamide derivative of Tranilast.

3. The stent of claim 2, wherein said diarylamide derivative is taken from the group:

4. The diarylamide derivative of claim 3, Formula II(a), where X=CO₂Et or CONH₂

5. The diarylamide derivative of claim 3, Formula II(b), where X=CO₂Et and Y=CH₂

6. The diarylamide derivative of claim 3 Formula II(c), where R₂=3,4-(OMe)₂, 3,4,5-(OMe)₃, or 2,3,4-(OMe)₃

7. The stent as recited in claim 1, wherein said coating is a polymer coating which contains said bioactive agent or agents.

8. The stent of claim 7, wherein said polymer coating is a bioerodeable coating.

9. The stent as recited in claim 7, wherein said polymer is selected from the group including Poly(D,L-lactic acid), Poly(L-lactic acid), Poly(D-lactic acid), Poly(glycolic acid), e-Caprolactone, or copolymers thereof, or mixtures thereof.

10. The stent as recited in claim 7, wherein the thickness of the coating on one of said plurality of support surfaces is different than the thickness of the coating on another one of said plurality of support surfaces, to thereby cause a proportionate increase or decrease in bioactive agent delivery in various regions of the stent.

11. The stent as recited in claim 7, wherein the polymer coating is applied only on selected portions of said support surfaces, forming islands of the polymer coating on the stent.

12. The stent as recited in claim 10, wherein the bioactive agent contained in one of said islands is different from the bioactive agent contained in another one of said islands.

13. The stent as recited in claim 11, wherein the thickness of one of said islands is different from the thickness of another one of said islands.

14. The stent as recited in claim 7, wherein at least one of said bioactive agents is in a crystalline form.

15. The stent as recited in claim 7, wherein the coating contains heparin in crystalline form as a bioactive agent.

16. The stent of claim 7, wherein said polymer coating acts as a drug storage reservoir for bioactive agents disposed therein, and wherein at least one of said bioactive agents is an antiplatelet, fibrinolytic, or thrombolytic agent in soluble crystalline form.

17. The stent of claim 16, wherein said antiplatelet, fibrinolytic, or thrombolytic agent is continuously eluted from the drug storage reservoir.

18. The stent as recited in claim 16, wherein said antiplatelet, fibrinolytic, or thrombolytic agent is heparin, aspirin, hirudin, ticlopadine(sp), eptifibatide, urokinase, streptokinase, tissue plasminogen activator (TPA), or abciximab, or a mixture thereof.

19. The stent of claim 1, wherein the stent contains a derivative of Tranilast of sufficient potency to be effective in controlling restenosis when incorporated in a polymer coating with a thickness of not more than 25 microns.

20. The stent as recited in claim 1, further comprising a primer polymer coating between said support surfaces and said coating.

21. The stent as recited in claim 20, wherein the primer polymer coating is formed substantially of poly(dichloro-para-xylylene).

22. The stent as recited in claim 1 further comprising a topcoat on said coating.

23. The stent as recited in claim 7, wherein said polymer is non-erodable polymer selected from the group including poly(vinyl alchohol) (PVA), EVA, EVOH, or copolymers thereof, or mixtures thereof.

26. The stent as recited in claim 7, wherein the support surfaces comprises outside support surfaces and inside support surfaces, the coating comprises an outside coating applied on the outside support surfaces and an inside coating applied on the inside support surfaces, wherein the inside coating forms one or more islands containing heparin in crystalline form.

24. A vascular stent containing a bioactive agent in an amount effective for reduction of restenosis, wherein the bioactive agent comprises one or more of the following related compounds:

25. The vascular stent of claim 24, wherein the bioactive agent is

27. A vascular stent containing a bioactive agent effective for the reduction of restenosis where the bioactive agent is a potent analogue or derivative of tranilast, which selectively controls smooth muscle cell proliferation, while not interfering to any substantial degree with proliferation of endothelial cells.

28. The stent as recited in claim 27, wherein the bioactive agent is a diarylamide derivative of tranilast.

29. A vascular stent having a stent support structure, and containing two biologically active agents in a coating on a surface of the stent support structure, wherein first one of said two agents is present in an effective quantity for control of restenosis, and second one of said two agents comprises an antiplatelet, fibrinolytic, or thrombolytic agent, wherein said antiplatelet, fibrinolytic, or thrombolytic agent, and is released for the same duration as the anti-restenosis agent.

30. The vascular stent as recited in claim 29, wherein the second agent is heparin, aspirin, hirudin, ticlopadine(sp), eptifibatide, urokinase, streptokinase, tissue plasminogen activator (TPA), or abciximab.

31. A fully bioerodable stent which is fabricated by deposition of a mixture of polymer and solvent on a preform, said polymer coating containing one or more bioactive agents.

32. The bioerodable stent of claim 31, wherein the preform is made of sucrose.

33. The bioerodable stent of claim 31, wherein the preform is soluble in a solvent which does not dissolve the polymer coating

34. The bioerodable stent of claim 31, wherein, after applying the polymer coating on the preform, the stent is placed in said solvent which dissolves the preform to free a completed stent structure.

35. The bioerodable stent of claim 31, wherein at least one of said bioactive agents is potent derivative of Tranilast.

36. The bioerodable stent of claim 31, wherein one of said bioactive agents is an antiplatelet, fibrinolytic, or thrombolytic agent in soluble crystalline form.

37. The bioerodable stent of claim 31, wherein one of said bioactive agents is an antiplatelet, fibrinolytic, or thrombolytic agent in soluble crystalline form.

38. The bioerodable stent of claim 31, wherein at least one of said bioactive agents is heparin, aspirin, hirudin, ticlopadine(sp), eptifibatide, urokinase, streptokinase, tissue plasminogen activator (TPA), or abciximab, or a mixture thereof.

39. The bioerodable stent of claim 31, wherein said bioactive agents are continuously eluted.

40. The bioerodeable stent of claim 35, wherein said potent derivative of Tranilast is a diarylamide derivative of Tranilast.

41. A method of coating a stent comprising an expandable stent body having a generally tubular shape, said stent body comprising a plurality of outside support surfaces and corresponding inner surfaces, said method comprising:

applying a polymer coating to said outside support surfaces, said coating including one or more bioactive agents and being applied from a delivery tube coupled to a pressurized source; and

coordinating said tube'"'"'s position along a longitudinal axis of said stent, and rotation of the stent about said longitudinal axis using a programmable controller.

42. The method as recited in claim 41, wherein the coating is applied from a distal end of the delivery tube, and a vertical height of the distal end of said tube is coordinated by said controller.

43. The method as recited in claim 41, wherein said step of applying a polymer coating is accomplished in a single pass.

44. The method as recited in claim 41, wherein the position of the tube is moved in small increments to sequentially apply the polymer solution across all of the interconnected outside surfaces of the stent support structure.

45. The method as recited in claim 41, wherein the position of the tube is moved continuously to sequentially apply the polymer solution across all of the interconnected outside surfaces of the stent support structure.

46. The method as recited in claim 41, wherein the thickness of the polymer coating is controlled by adjusting one or more of the following:

the speed of rotation of the tube, the dwell time of the distal end of the tube at specific areas on the stent, the pressure of the pressurized source, the speed of movement of the distal end of the delivery tube, the vertical height of the distal end, the viscosity of the polymer solution, or the types of polymer and solvent.

47. The method as recited in claim 41, wherein the step of applying a polymer coating to said outside support surfaces is controlled, so that the thickness of the polymer coating on the inner surfaces is significantly smaller than thickness of the polymer coating on the outside support surfaces.

48. The method as recited in claim 41, wherein the step of applying a polymer coating to said outside support surfaces is controlled, so that the polymer coating forms isolated islands on the outside support surfaces.

49. The method as recited in claim 48, wherein one of said islands contains a bioactive agent different from that contained in another one of said islands.